[Changes and significance of endogenous tissue plasminogen activators in cerebral hypoxia-ischemia in neonatal rats].
OBJECTIVE
The mechanism of neonatal hypoxic-ischemic brain damage (HIBD) remains unclear and effective treatment approach is limited for this disorder. Many studies have shown that tissue-type plasminogen activator (tPA) plays an important role in nervous system. This study investigated the effect of tPA in HIBD in neonatal rats.


METHODS
Seven-day-old Wistar rat pups were used for the Rice-Vannucci model of neonatal hypoxia-ischemia (HI). Brain samples were collected 1, 4, and 24 hrs after HI. FITC-Dextran was injected into the left ventricle of pups after HI to observe reperfusion defects of the neonatal brain. RT-PCR and tPA zymogram were used to detect the expression and activity of tPA. Double immunostaining, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DAPI staining were used to detect the expression of integrin GPIIb and fibrin and neuronal apoptosis.


RESULTS
FITC-Dextran perfusion analysis indicated there was obvious infarct area in the neonatal brain and the expression of integrin GPIIb and fibrin increased significantly 1 hr after HI compared with the contralateral side. The infarct area decreased and the expression of integrin GPIIb and fibrin were reduced 4 hrs after HI. The expression and activity of tPA increased significantly in neonatal rats after HI, and peaked at 4 hrs after HI. The number of apoptotic neural cells increased progressively with the prolonged reperfusion time following HI.


CONCLUSIONS
The increase of tPA in the acute phase after HIBD may be helpful to clot dissolving, but it induces neuronal apoptosis and aggravates brain injury.
Yu
Dan
D
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Mao
Meng
M
Lei
Ming-Yu
MY
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D005337:Fibrin / Q000032:analysis; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D040201:Platelet Membrane Glycoprotein IIb / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000502:physiology*
D040201:Platelet Membrane Glycoprotein IIb; D005337:Fibrin; D010959:Tissue Plasminogen Activator